Parkinson's Cure Journey

Landmark 112 · Trial in people

AAV-AADC gene therapy

Two small trials, in 10 and 15 people, had no comparison group. Dopamine-making rose and symptoms eased. It treats symptoms and does not slow the disease.

In short

Injecting a virus carrying the AADC gene into the putamen raised dopamine-making in the brain and helped symptoms in two small open-label trials (10 and 15 people); the later Voyager phase 1b and sham-controlled trial, and the end of the Parkinson's programme in 2021, are in landmark 305.

What it is
Trial in people
Outcome
Passed this stage
When
2004–2019
Approach
Replace or repair what's lost
Research lane
Gene therapy & delivery
Trial registry
NCT00229736
Last checked
19 Oct 2026

The research record

This is the project's file for this landmark, as written and checked. Sources are listed at the end; anything not yet confirmed is marked "Not yet verified".

Who

Chadwick Christine, Krystof Bankiewicz, Paul Larson, Michael Aminoff and colleagues at UCSF. The 2009 trial (NCT00229736, started November 2004) was sponsored by Genzyme; the 2019 trial (NCT01973543, started October 2013) by Voyager Therapeutics, later Neurocrine Biosciences.

What happened

AADC is the enzyme that turns levodopa into dopamine, and it declines as dopamine neurons die. In 2009 Christine et al. gave 10 people with moderately advanced Parkinson's an AAV2 vector carrying the human AADC gene, infused into both putamens (the striatal region that needs dopamine). Putamen uptake of an AADC PET tracer rose about 30% (low dose) and 75% (high dose), and motor scores improved in this open-label study. Three brain bleeds occurred along the catheter path, attributed to surgery. The authors rated the evidence "class IV" (no control group) and reported about a 30% improvement in UPDRS scores. Christine et al., Neurology 2009;73:1662-1669.

In 2019 the same group reported an MRI-guided phase 1 (VY-AADC01, AAV2; 15 people in three cohorts of five): putamen coverage by the infusion was 21%, 34% and 42%; PET enzyme activity rose 13%, 56% and 79%; and antiparkinsonian medication use fell 15%, 33% and 42% at 6 months. At 12 months, ON-time without troublesome dyskinesia rose by 1.6, 3.3 and 1.5 hours (Annals of Neurology 85:704-714). Three-year follow-up of the same trial reported no serious adverse events attributed to the vector and 21–30% lower medication needs in the two higher-dose cohorts (Neurology 2022;98:e40-e50). The follow-on Phase 1b and the sham-controlled RESTORE-1 trial, including the 2020 FDA hold and the 2021 end of the programme, are in landmark 305.

Why it moved us toward a cure

Honest framing: this treats symptoms by restoring dopamine-making, not by slowing the disease, so it is not itself a cure route. It matters because it proved that gene therapy can be given to the human putamen under MRI guidance, a delivery method reused by later programmes such as GDNF gene therapy (landmark 39).

Delivery relied on MRI-guided convection-enhanced infusion (landmark 253).

Outcome

Advanced to a sham-controlled trial, which ended the Parkinson's programme (landmark 305). Elsewhere, eladocagene exuparvovec (Upstaza) was authorised in the EU on 18 July 2022 and Kebilidi received FDA accelerated approval on 13 November 2024, both for AADC deficiency, a rare inherited disease.

Sources

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